The process of angiogenesis involves coordinated endothelial cell (EC) proliferation, invasion, migration, and tube formation. This process is known to be induced by vascular growth factors and its receptors in coordination with extracellular matrix interacting molecules such as integrins. Integrins are heterodimeric transmembrane receptors, which play central roles in cell adhesion, migration, proliferation, differentiation and programmed cell death. αvβ3 integrin is a major integrin expressed on proliferating endothelial cells during angiogenesis and vascular remodeling. The disruption of αvβ3 integrin ligation either by blocking antibody (LM609 or Vitaxin) or by cyclic peptide antagonists (RGD) prevents blood vessel formation in mouse retina, rabbit cornea, chick chorioallantoic membrane, and human skin transplanted onto athymic mice. More importantly, function-blocking anti-β3 antibody that recognizes at least three integrins (αIIbβ3, αvβ3 and αMβ2) has been shown to be beneficial in high risk angioplasty patients in part due to the blockade of αvβ3. In the studies on the role of αvβ3 in tumor vasculature and survival, histological examination of the tumor tissue treated with the αvβ3 blockers revealed reduction not only in the tumor cell viability but also in the vascular density.
Mice lacking αv integrin showed relatively normal blood vessel development αv integrin knockout mice died at early stages of development due to extensive vasculature). Furthermore, studies using β3 and β5 null mice demonstrated an enhanced tumor growth, tumor angiogenesis and VEGF-A-induced vascular permeability due to the elevated levels of VEGFR-2 on EC. Therefore, it has been concluded that αvβ3 and αvβ5 integrin function as the negative regulators of angiogenesis by restricting the VEGF receptor-2 expression.